Cytogenetics and the evolution of medical genetics
Vanda Sues FDA Again, This Time Over Off-Label Use Of Hetlioz For Jet Lag
Despite suffering a series of rebuffs from the FDA, Vanda Pharmaceuticals is continuing to fight for sedative Hetlioz, suing the regulator last week to use the drug off-label for jet lag.
In the complaint, filed April 9 with the U.S. District Court for the Southern District of Texas, Vanda slammed the regulator's "restrictive regulatory regime," and alleged a violation of the company's First Amendment right to provide doctors with relevant information about its drugs, as per reporting from Fierce Pharma.
Hetlioz is a sedative that was first approved in 2014 for non-24-hour sleep-wake disorder and was later granted a label expansion to cover sleep disorders for the rare disease Smith-Magenis syndrome. At issue is Vanda's desire to promote Hetlioz in off-label uses.
Doctors can legally prescribe approved drugs off label for uses that have yet to be cleared by the FDA, but the agency limits the information that companies can share about unapproved uses. As per a recent guidance document, drug sponsors "should provide and appropriately present all information necessary" to allow healthcare providers to better assess the benefits and risks of the unapproved uses.
Companies should also be "truthful and non-misleading," according to the FDA guidance. Their communications to doctors should emphasize that the product has not yet been approved by the FDA for the use and include details regarding known contraindications and safety risks.
Vanda took issue with these restrictions, noting in its press release that they "prevent pharmaceutical manufacturers from sharing their new discoveries with doctors" for fear of being misleading, Fierce reported. The biotech added that while they have a "credible fear" of being sanctioned for sharing Hetlioz data to doctors, it's the patients who "ultimately suffer" from the FDA's limitations.
Also in the court complaint, Vanda provided detailed clinical information about Hetlioz's efficacy and safety in patients with jet lag, for which the drug is not approved. Vanda insists that the data support the drug's use in this indication. The biotech is asking the court to declare its information about off-label Hetlioz use to be truthful.
Vanda's latest lawsuit puts even more pressure on an already-strained relationship with the FDA. In July 2019, the regulator rejected Vanda's bid for approval of Hetlioz in jetlag, a decision which the biotech appealed. Vanda asked for a hearing on the verdict in July 2022, but after months of not hearing back, the biotech sued the regulator for not being able to stick to its mandated timeline.
The FDA last year also rejected Vanda's application for the NK-1R antagonist tradipitant for gastroparesis, a move that the biotech again contested. In September 2024, Vanda argued that the regulator's verdict "generally disregarded the evidence provided." The biotech again blasted the FDA's timeline—the decision on tradipitant was delayed by more than 185 days, which violates the Federal Drug and Cosmetic Act's 180-day deadline, Vanda argued.
In January, the biotech escalated the matter to then-FDA Commissioner Robert Califf. In a letter, Vanda called attention to the "culture of obfuscation and closemindedness" at the agency, which it faults for the lack of transparency regarding tradipitant's rejection. A few days after the letter, the FDA finally provided Vanda with a justification for the rejection and gave the company the chance to request a hearing.
Tasimelteon For Treating Sleep Disturbance Associated With Smith-Magenis Syndrome [TSID12191]
Status Awaiting development Technology type Medicine Decision Selected Reason for decision Anticipate the topic will be of importance to patients, carers, professionals, commissioners and the health of the public to ensure clinical benefit is realised, inequalities in use addressed, and help them make the best use of NHS resources Process STA Standard ID number 12191Project Team Project lead Danielle Lees Email enquiries Timeline
Key events during the development of the guidance:
Date Update 15 April 2025 Awaiting development. Status change linked to Topic Selection Decision being set to SelectedFor further information on our processes and methods, please see our CHTE processes and methods manual
Molecular Mechanism For Duplication 17p11.2— The Homologous Recombination Reciprocal Of The Smith-Magenis Microdeletion
Lupski, J.R. Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genet. 14, 417–422 (1998).
Lupski, J.R. Charcot-Marie-Tooth disease: lessons in genetic mechanisms. Mol. Med. 4, 3–11 ( 1998).
Chen, K.-S., Potocki, L. & Lupski, J.R. The Smith-Magenis syndrome [del(17)p11.2]: clinical review and molecular advances. Ment. Retard. Dev. Disabil. Res. Rev. 2, 122–129 ( 1996).
Greenberg, F. Et al. Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2). Am. J. Med. Genet. 62, 247–254 (1996).
Greenberg, F. Et al. Molecular analysis of the Smith-Magenis syndrome: a possible contiguous-gene syndrome associated with del(17)(p11.2). Am. J. Hum. Genet. 49, 1207–1218 (1991).
Guzzetta, V. Et al. Somatic cell hybrids, sequence-tagged sites, simple repeat polymorphisms, and yeast artificial chromosomes for physical and genetic mapping of proximal 17p. Genomics 13, 551– 559 (1992).
Juyal, R.C. Et al. Molecular analyses of 17p11.2 deletions in 62 Smith-Magenis syndrome patients. Am. J. Hum. Genet. 58, 998–1007 (1996).
Chen, K.-S. Et al. Homologous recombination of a flanking repeat gene cluster is a mechanism for a common contiguous gene deletion syndrome. Nature Genet. 17, 154–163 (1997).
Osborne, L.R. Et al. PMS2-related genes flank the rearrangement breakpoints associated with Williams syndrome and other diseases on human chromosome 7. Genomics 45, 402–406 ( 1997).
Pérez Jurado, L.A., Peoples, R., Kaplan, P., Hamel, B.C.J. & Francke, U. Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth. Am. J. Hum. Genet. 59, 781–792 (1996).
Pérez Jurado, L.A. Et al. A duplicated gene in the breakpoint regions of the 7q11.23 Williams-Beuren syndrome deletion encodes the initiator binding protein TFII-I and BAP-135, a phosphorylation target of BTK. Hum. Mol. Genet. 7, 325–334 ( 1998).
Christian, S.L., Fantes, J.A., Mewborn, S.K., Huang, B. & Ledbetter, D.H. Large genomic duplicons map to sites of instability in the Prader-Willi/Angelman syndrome chromosome region (15q11–q13). Hum. Mol. Genet. 8, 1025 –1037 (1999).
Amos-Landgraf, J.M. Et al. Chromosome breakage in Prader-Willi and Angelman syndromes involves recombination between large, transcribed repeats at proximal and distal breakpoints. Am. J. Hum. Genet. 65, 370–386 (1999).
Edelmann, L., Pandita, R.K. & Morrow, B.E. Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome. Am. J. Hum. Genet. 64, 1076–1086 ( 1999).
Edelmann, L. Et al. A common molecular basis for rearrangement disorders on chromosome 22q11. Hum. Mol. Genet. 8, 1157– 1167 (1999).
Patel, P.I. Et al. The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot-Marie-Tooth disease type 1A. Nature Genet. 1, 159–165 (1992).
Chen, K.-S. Et al. The human homologue of the Drosophila melanogasterflightless-I gene ( fliI) maps within the Smith-Magenis microdeletion critical region in 17p11.2. Am. J. Hum. Genet. 56, 175– 182 (1995).
Elsea, S.H. Et al. Definition of the critical interval for Smith-Magenis syndrome . Cytogenet. Cell Genet. 79, 276– 281 (1997).
Zhao, Q., Chen, K.-S., Bejjani, B.A. & Lupski, J.R. Cloning, genomic structure, and expression of mouse ring finger protein gene Znf179. Genomics 49, 394– 400 (1998).
Roa, B.B. Et al. Duplication of the PMP22gene in 17p partial trisomy patients with Charcot-Marie-Tooth type-1A neuropathy. Hum. Genet. 97, 642–649 (1996).
Kozma, C., Meck, J.M., Loomis, K.J. & Galindo, H.C. De novoduplication of 17p [dup(17)(p12→p11.2)]: report of an additional case with confirmation of the cytogenetic, phenotypic, and developmental aspects. Am. J. Med. Genet. 41, 446–450 (1991).
Lopes, J. Et al. Sex-dependent rearrangements resulting in CMT1A and HNPP. Nature Genet. 17, 136–137 (1997).
Buiting, K. Et al. Expressed copies of the MN7 (D15F37) gene family map close to the common deletion breakpoints in the Prader-Willi/Angelman syndromes . Cytogenet. Cell Genet. 81, 247– 253 (1998).
Repetto, G.M., White, L.M., Bader, P.J., Johnson, D. & Knoll, J.H.M. Interstitial duplications of chromosome region 15q11q13: clinical and molecular characterization. Am. J. Med. Genet. 79, 82–89 (1998).
Shaffer, L.G., Kennedy, G.M., Spikes, A.S. & Lupski, J.R. Diagnosis of CMT1A duplications and HNPP deletions by interphase FISH: implications for testing in the cytogenetics laboratory. Am. J. Med. Genet. 69, 325–331 ( 1997).
Pentao, L., Wise, C.A., Chinault, A.C., Patel, P.I. & Lupski, J.R. Charcot-Marie-Tooth type 1A duplication appears to arise from recombination at repeat sequences flanking the 1.5 Mb monomer unit. Nature Genet. 2, 292– 300 (1992).
Potocki, L. Et al. DNA rearrangements on both homologues of chromosome 17 in a mildly delayed individual with a family history of autosomal dominant carpal tunnel syndrome. Am. J. Hum. Genet. 64, 471–478 (1999).
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